The goal of this K23 Mentored Patient-Oriented Research Career Development Award is to develop Heather Greenlee, ND, PhD's expertise in the safety and efficacy of antioxidant supplement use during breast cancer adjuvant therapy. The use of antioxidant supplements during cancer radiation therapy and chemotherapy is controversial because the short- and long-term effects of this use are largely unknown. For example, coenzyme Q10 (C0QIO), a lipid soluble antioxidant, has been hypothesized to decrease doxorubicin-induced cardiotoxicity. However it is unknown if using an antioxidant supplement such as CoQ 10 during doxorubicin treatment would decrease doxorubicin's long-term treatment efficacy. Despite this controversy, an estimated 45-80% of breast cancer patients use antioxidant supplements during their treatment. Well designed observational studies and clinical trials are needed to elucidate the effects of these agents. In this proposed award, I will receive focused mentorship and training from established investigators at Columbia University Medical Center in the areas of oncology clinical trials (Dawn Hershman, MD, MS), pathways of oxidative stress (Regina Santella, PhD), and cancer prevention and control (Alfred Neugut, MD, PhD). I will complete coursework and training in molecular epidemiology, biostatistical methods, clinical trial design, and cancer prevention and control. Three complementary studies are proposed to study the early and late effects of antioxidant supplement use during adjuvant treatment for breast cancer. Study one is a phase I randomized, placebo-controlled, pharmacokinetic study on the effect of C0QIO on doxorubicin metabolism during breast cancer treatment. Study Two is a phase Mb randomized, placebo-controlled trial on the effect of C0QIO preventing doxorubicin-induced cardiotoxicity during breast cancer treatment. Study Three is a nested cohort study within the Pathways Study examining the effects of antioxidant supplement use during breast cancer chemotherapy, radiation therapy, and hormonal therapy on breast cancer recurrence and survival. The Pathways Study is an NCI-funded prospective cohort study of breast cancer patients diagnosed within Kaiser Permanente Northern California (n=3,000; PI: Lawrence Kushi, ScD). At the completion of this proposed award, I will be an independent researcher and expert in the use of clinical trials and observational studies to examine the short- and long-term effects of antioxidant supplement use during breast cancer treatment, and will be fully prepared to pursue NCI R01 funding. RELEVANCE: A large proportion of cancer patients use antioxidant supplements during cancer treatment. However, the eariy and late effects of this use are largely unknown, and may be harmful. Well trained investigators are needed to conduct observational studies and clinical trials in this area to elucidate the short- and long-term effects of these agents.